Scott A Mosley1, J Kevin Hicks2, Diane G Portman3, Kristine A Donovan3, Priya Gopalan4, Jessica Schmit4, Jason Starr4, Natalie Silver5, Yan Gong1, Taimour Langaee1, Michael Clare-Salzler6, Petr Starostik7, Young D Chang3, Sahana Rajasekhara3, Joshua E Smith3, Heloisa P Soares8, Thomas J George4, Howard L McLeod2, Larisa H Cavallari9. 1. Department of Pharmacotherapy and Translational Research, College of Pharmacy, University of Florida, Gainesville, FL, USA; Center for Pharmacogenomics, University of Florida, Gainesville, FL, USA. 2. DeBartolo Family Personalized Medicine Institute, Department of Individualized Cancer Management, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA. 3. Department of Supportive Care Medicine, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA. 4. Department of Medicine, College of Medicine, University of Florida, Gainesville, FL, USA. 5. Department of Otolaryngology, College of Medicine, University of Florida, Gainesville, FL, USA. 6. Department of Medicine, College of Medicine, University of Florida, Gainesville, FL, USA; Department of Pathology, Immunology & Laboratory Medicine, College of Medicine, University of Florida, Gainesville, FL, USA. 7. Department of Pathology, Immunology & Laboratory Medicine, College of Medicine, University of Florida, Gainesville, FL, USA. 8. Department of Gastrointestinal Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA. 9. Department of Pharmacotherapy and Translational Research, College of Pharmacy, University of Florida, Gainesville, FL, USA; Center for Pharmacogenomics, University of Florida, Gainesville, FL, USA; Clinical and Translational Science Institute, University of Florida, Gainesville, FL, USA. Electronic address: lcavallari@cop.ufl.edu.
Abstract
INTRODUCTION: Pain is one of the most burdensome symptoms associated with cancer and its treatment, and opioids are the cornerstone of pain management. Opioid therapy is empirically selected, and patients often require adjustments in therapy to effectively alleviate pain or ameliorate adverse drug effects that interfere with quality of life. There are data suggesting CYP2D6 genotype may contribute to inter-patient variability in response to opioids through its effects on opioid metabolism. Therefore, we aim to determine if CYP2D6 genotype-guided opioid prescribing results in greater reductions in pain and symptom severity and interference with daily living compared to a conventional prescribing approach in patients with cancer. METHODS:Patients with solid tumors with metastasis and a self-reported pain score ≥ 4/10 are eligible for enrollment and randomized to agenotype-guided or conventional pain management strategy. For patients in the genotype-guided arm, CYP2D6 genotype information is integrated into opioid prescribing decisions. Patients are asked to complete questionnaires regarding their pain, symptoms, and quality of life at baseline and 2, 4, 6, and 8 weeks after enrollment. The primary endpoint is differential change in pain severity by treatment strategy (genotype-guided versus conventional pain management). Secondary endpoints include change in pain and symptom interference with daily living. CONCLUSION: Pharmacogenetic-guided opioid selection for cancer pain management has potential clinical utility, but current evidence is limited to retrospective and observational studies. Precision Medicine Guided Treatment for Cancer Pain is a pragmatic clinical trial that seeks to determine the utility of CYP2D6 genotype-guided opioid prescribing in patients with cancer.
RCT Entities:
INTRODUCTION:Pain is one of the most burdensome symptoms associated with cancer and its treatment, and opioids are the cornerstone of pain management. Opioid therapy is empirically selected, and patients often require adjustments in therapy to effectively alleviate pain or ameliorate adverse drug effects that interfere with quality of life. There are data suggesting CYP2D6 genotype may contribute to inter-patient variability in response to opioids through its effects on opioid metabolism. Therefore, we aim to determine if CYP2D6 genotype-guided opioid prescribing results in greater reductions in pain and symptom severity and interference with daily living compared to a conventional prescribing approach in patients with cancer. METHODS:Patients with solid tumors with metastasis and a self-reported pain score ≥ 4/10 are eligible for enrollment and randomized to a genotype-guided or conventional pain management strategy. For patients in the genotype-guided arm, CYP2D6 genotype information is integrated into opioid prescribing decisions. Patients are asked to complete questionnaires regarding their pain, symptoms, and quality of life at baseline and 2, 4, 6, and 8 weeks after enrollment. The primary endpoint is differential change in pain severity by treatment strategy (genotype-guided versus conventional pain management). Secondary endpoints include change in pain and symptom interference with daily living. CONCLUSION: Pharmacogenetic-guided opioid selection for cancer pain management has potential clinical utility, but current evidence is limited to retrospective and observational studies. Precision Medicine Guided Treatment for Cancer Pain is a pragmatic clinical trial that seeks to determine the utility of CYP2D6 genotype-guided opioid prescribing in patients with cancer.
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